IRX-2 Regimen in Treating Women With Cervical Squamous Intraepithelial Neoplasia 3 or Squamous Vulvar Intraepithelial Neoplasia 3

NCT03267680 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: 5GYN-16-2NCI-2017-01402P30CA014089
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

This randomized phase II trial studies how well an IRX-2 Regimen works in treating women with cervical squamous intraepithelial neoplasia 3 or squamous vulvar intraepithelial neoplasia 3. The IRX-2 Regimen consists of a single dose of cyclophosphamide, followed by 21 days of indomethacin, zinc-containing multivitamins, and omeprazole. IRX-2, a human cell-derived biologic with multiple active cytokine components, may act as an immune booster to stimulate the immune system. Giving cyclophosphamide and IRX-2 may work better at treating cervical squamous intraepithelial neoplasia or squamous vulvar intraepithelial neoplasia.

Conditions

Cervical Squamous Cell Carcinoma In Situ; Vulvar High Grade Squamous Intraepithelial Lesion

Outcome Measures

Primary Outcomes (1)

• Pathologic Response

  Complete Response (CR) is defined as absence of intraepithelial neoplasia, Partial Response (PR) is defined as a lower grade of dysplasia than present at baseline (for example, grade 3 decreasing to grade 1).

  Week 25

Secondary Outcomes (1)

• Incidence of Adverse Events of IRX-2 Administration

  Up to 30 months

Study Arms (2)

Arm I (IRX-2)

EXPERIMENTAL

Patients receive cyclophosphamide IV on day 1 and IRX-2 via submucosal injections in the cervix or SC for vulvar lesions on days 4-7. Patients also receive indomethacin PO TID, zinc-containing multivitamins PO QD and omeprazole PO on days 1-21. Treatment repeats every 6 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Beginning week 25, patients undergo surgical resection.

Drug: Cyclophosphamide; Drug: Indomethacin; Biological: IRX-2; Other: Laboratory Biomarker Analysis; Dietary Supplement: Multivitamin; Drug: Omeprazole; Procedure: Therapeutic Conventional Surgery

Arm II (placebo)

ACTIVE COMPARATOR

Patients receive cyclophosphamide IV on day 1 and placebo via submucosal injections in the cervix or SC for vulvar lesions on days 4-7. Patients also receive indomethacin PO TID, zinc-containing multivitamins PO QD and omeprazole PO on days 1-21. Treatment repeats every 6 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Beginning week 25, patients undergo surgical resection.

Drug: Cyclophosphamide; Drug: Indomethacin; Other: Laboratory Biomarker Analysis; Dietary Supplement: Multivitamin; Drug: Omeprazole; Other: Placebo; Procedure: Therapeutic Conventional Surgery

Interventions

Cyclophosphamide DRUG

Given IV

Arm I (IRX-2); Arm II (placebo)

Indomethacin DRUG

Given PO

Arm I (IRX-2); Arm II (placebo)

IRX-2 BIOLOGICAL

Given via submucosal injection or SC

Arm I (IRX-2)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (IRX-2); Arm II (placebo)

Multivitamin DIETARY_SUPPLEMENT

Given zinc-containing multivitamin PO

Also known as: Geritol, Vitamin Supplements (NOS)

Arm I (IRX-2); Arm II (placebo)

Omeprazole DRUG

Given PO

Arm I (IRX-2); Arm II (placebo)

Placebo OTHER

Given via submucosal injections or SC

Also known as: placebo therapy, sham therapy

Arm II (placebo)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgical resection

Arm I (IRX-2); Arm II (placebo)

Eligibility Criteria

• Age: 25 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed squamous CIN 3, or VIN 3 (usual type only)
• The subject is either surgically sterile, postmenopausal, or agrees to practice an effective method of birth control as determined by the investigator (to be continued throughout the study period), except that subjects with CIN 3 are not permitted to use a cervical cap or diaphragm for contraception
• White blood cell \> 2,500/ mcL (\> 2.5 x 10\^9/L)
• Absolute neutrophil count \> 1,000/ microliter (\> 1 x 10\^9/L)
• Platelet count \> 75,000/ mcL (\> 75 x 10\^9/L)
• Hemoglobin \>= 8 g/dL (\>= 80 g/L) (subjects who have received a transfusion or erythropoietin up to one week prior to receiving the first dose of cyclophosphamide are eligible for the study)
• International normalized ration (INR) or prothrombin time (PT) \< 1.5 x ULN (upper limit of normal)
• Activated partial thromboplastin time (aPTT) \< 1.5 x ULN
• Serum creatinine \< 1.5 x ULN
• Total bilirubin \< 2.0 x ULN unless thought to be related to inherited bilirubin conjugation disorder (ie Gilbert?s disease)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2.5 x ULN
• The subject is geographically accessible for ongoing follow-up and is committed to comply with the designated visits
• The subject is capable of understanding and complying with the protocol and has signed the enrollment informed consent form at screening

You may not qualify if:

• For subjects with cervical dysplasia: evidence of atypical glandular cells or adenocarcinoma in situ (ACIS) based on cervical cytology, colposcopy or biopsy
• For subjects with either cervical or vulvar squamous dysplasia: evidence of microinvasive squamous carcinoma based on cytology, colposcopy or biopsy
• Pregnancy or lactation
• Allergy to ciprofloxacin or other quinolones (because ciprofloxacin is used in preparation of IRX-2)
• Allergy to indomethacin (a necessary component of the regimen) or to acetylsalicylic acid (aspirin) due to likely allergy cross-reaction
• Aldara (imiquimod) for the topical treatment of lower genital tract warts or dysplasia within 3 months of study enrollment
• Known to be positive for human immunodeficiency virus-1 (HIV-1) antibody, human immunodeficiency virus-2 (HIV-2) antibody, hepatitis B surface antigen, or hepatitis C virus antibody
• Known to have other immunodeficiency diseases, including cellular immunodeficiencies, hypogammaglobulinemia, or dysgammaglobulinemia
• Immunotherapy (eg, interferons, tumor necrosis factor, interleukins) or biological response modifiers (granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, macrophage colony-stimulating factor) or any investigational drug within 3 months of study enrollment
• Concurrent treatment with systemic corticosteroids at a dose of \>= 5 mg/day of prednisone (or equivalent)
• Subjects should not take aspirin (except for low-dose aspirin as prescribed for vascular disease) or other non-prescribed, non-steroidal anti-inflammatory agents from randomization to surgery
• An infectious process or any other significant illness such as an autoimmune disease or advanced age that in the opinion of the investigator would compromise the subject?s ability to mount an immune response
• Impaired hepatic, renal or hematological function, evidenced by:
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin \>= 2 times upper limit of normal (ULN),
• Serum creatinine \>= 2 times ULN, or

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator
• Brooklyn ImmunoTherapeutics, LLC: collaborator

Study Sites (2)

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of Oklahoma Health Sciences Center, Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

MeSH Terms

Conditions

Uterine Cervical Dysplasia

Interventions

Cyclophosphamide; Indomethacin; IRX 2; Geritol; Omeprazole

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Benzimidazoles

Results Point of Contact

• Title: Tali Homsey
• Organization: University of Southern California

tali.homsey@med.usc.edu

3238650430

Study Officials

• Lynda Roman, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2017
• First Posted: August 30, 2017
• Study Start: November 8, 2017
• Primary Completion: August 4, 2023
• Study Completion: March 13, 2024
• Last Updated: April 13, 2025
• Results First Posted: April 13, 2025

Record last verified: 2025-03

Locations

US (2)